title: Intermedin enhances sympathetic outflow via receptor-mediated cAMP/PKA signaling pathway in nucleus tractus solitarii of rats.
abstract: Direct administration of intermedin (IMD) into the brain elicits cardiovascular effects different from the systemic administration. Nucleus tractus solitarii (NTS) is an important region for the cardiovascular regulation. The present study was designed to determine the effect of IMD on modulating the sympathetic outflow and its related molecular mechanism in the NTS. Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in anesthetized rats. Site-specific microinjection of IMD (20pmol) bilaterally into the NTS significantly increased RSNA and MAP. IMD-evoked increases of RSNA and MAP were almost abolished by pretreatment with receptor antagonist ADM22-52, an adenylyl cyclase (AC) inhibitor SQ22536, or a protein kinase A (PKA) inhibitor Rp-cAMP. However, pretreatment with another receptor antagonist calcitonin gene-related peptide (CGRP)8-37 did not suppress the increases of RSNA and MAP induced by IMD. Furthermore, IMD increased the cyclic adenosine monophosphate (cAMP) level, which was inhibited by ADM22-52 pretreatment in the NTS. These results suggest that IMD participates in the sympathetic nerve activity and central regulation of the cardiovascular system and a receptor-mediated cAMP/PKA signaling pathway is involved in IMD-induced effects in the NTS.
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Hai-Jian
authors.initials: HJ
authors.lastname: Sun
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
authors.forename: Jue-Jin
authors.initials: JJ
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Chao-Shu
authors.initials: CS
authors.lastname: Tang
authors.forename: Ye-Bo
authors.initials: YB
authors.lastname: Zhou
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D053607:Adrenomedullin / Q000494:pharmacology*; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005728:Ganglia, Sympathetic / Q000098:blood supply / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007276:Injections, Intraventricular; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D017552:Solitary Nucleus / Q000187:drug effects* / Q000502:physiology; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; C499411:Adm2 protein, rat; D009479:Neuropeptides; D010446:Peptide Fragments; D013873:Thionucleotides; C104782:adrenomedullin (22-52); C058636:calcitonin gene-related peptide (8-37); D053607:Adrenomedullin; C017759:9-(tetrahydro-2-furyl)-adenine; C016957:adenosine-3',5'-cyclic phosphorothioate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; D000225:Adenine; D015740:Calcitonin Gene-Related Peptide
keywords: AC; AM; BP; CGRP; CNS; CRLR; HR; IMD; Intermedin; MAP; NTS; Nucleus tractus solitarii; PKA; Protein kinase A; RAMP; RSNA; SNA; Sympathetic outflow; adenylyl cyclase; adrenomedullin; blood pressure; cAMP; calcitonin gene-related peptide; calcitonin receptor-like receptor; central nervous system; cyclic adenosine monophosphate; heart rate; icv; intermedin; intracerebroventricularly; mNTS; mean arterial pressure; medial subnucleus of the nucleus tractus solitarii; nucleus tractus solitarii; protein kinase A; receptor-activity modifying protein; renal sympathetic nerve activity; sympathetic nerve activity